Twin Study of Chronic Widespread Pain

PI: Niloofar Afari
Project Number: 5R01AR051524
Project Dates: 9/25/2005–7/31/2011

Chronic widespread pain (CWP) occurs in 4-13% of people and is one of the defining characteristics of Fibromyalgia (FM). Although tender points were originally considered as essential to the diagnosis of FM, it is now felt that they reflect pain severity and distress, and that FM lies at one end of the CWP continuum. To truly understand the pathogenesis of CWP, it would be optimal to study the entire spectrum of individuals who have this symptom. Another critical issue in the mechanistic study of CWP is what to study. Over the past two decades, FM researchers have described abnormalities in various components of the central nervous system and high rates of psychological co-morbidities and other chronic multi-symptom illnesses. The role and significance of each of these factors in predisposing to the illness, directly causing the symptoms, or occurring as a consequence of the condition, are unclear.

The complexity of FM and the continuum of CWP have led us to develop a theoretical model of CWP that is synergistic and multidimensional. Predisposing factors are of particular interest in this model since these represent premorbid risk or protective factors that relate to the development of CWP. Further, predisposing factors can be differentiated from illness-associated features that occur as a consequence of the condition.

A co-twin control study is a powerful means for examining specific hypotheses about the etiology and consequences of CWP derived from the theoretical model. Twenty-one MZ and 21 DZ twin pairs discordant for CWP, along with 22 MZ and DZ pain-free control twin pairs will be recruited from the population-based University of Washington Twin Registry. Twin will undergo an intensive evaluation of the autonomic nervous system (ANS) function, hypothalamic-pituitary-adrenal (HPA) axis function, exercise capacity, sleep and activity levels, evoked pain processing, and psychiatric and psychosocial factors involved in CWP.

There are 2 Specific Aims: 1) Assess similarities and differences in ANS function, HPA axis function, exercise capacity, sleep and activity levels, evoked pressure pain sensitivity, and psychiatric and psychosocial factors between female twins with CWP and their pain-free co-twins. 2) Determine if the association between CWP and the above illness characteristics is due to confounding by genetics or common environmental factors by comparing CWP-discordant MZ female twin pairs with CWP-discordant DZ and pain-free MZ and DZ pairs. Additionally, investigating the pattern of differences between twin groups can help to distinguish factors that are predisposing to CWP and those that occur after the onset of the illness.